小梁网
细胞外基质
细胞内
细胞外
地塞米松
化学
细胞生物学
内分泌学
生物
青光眼
神经科学
作者
Canying Liu,Jiahui Tang,Yuze Chen,Qi Zhang,Jicheng Lin,Siting Wu,Jiaxu Han,Zhe Liu,Caiqing Wu,Yehong Zhuo,Yiqing Li
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2024-03-25
标识
DOI:10.1152/ajpcell.00725.2023
摘要
Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It's widely agreed that glucocorticoids impact the expression of Matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn 2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn 2+ significantly decreased and accompanied by impaired extracellular Zn 2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIP) and metallothionein. ZIP8 knockdown impaired extracellular Zn 2+ uptake, but Zn 2+ chelation didn't affect ZIP8 expression. Resembling DEX's effects, chelating Zn 2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn 2+ to DEX-treated cells ameliorated these outcomes. Inspiringly, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.
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